Stabilin-1(STAB1/FEEL1/KIAA0246), is a type I transmembrane protein with two main functions: “scavenger receptor function”and “cell adhesion function''. It is primarily expressed on non-parenchymal cells such as liver sinusoidal endothelial cells, lymph node sinusoidal endothelial cells, and macrophages, playing a crucial role in maintaining homeostasis.

STAB1 Expression distribution

STAB1 is mainly expressed at high levels in the spleen, lymph nodes, liver and placenta, and is also expressed in endothelial cells.

(Data source: proteinatlas)

STAB1 Structure

STAB1 The length 2570 of STAB1 the gene encoding aa, with a molecular weight of about 275.4 kDa typeⅠtransmembrane protein, composed of three parts: intracellular region, transmembrane region and extracellular region.

Extracellular domain (26-2478 aa): a) Fasciclin-like domain (FA58C domains): Composed of repetitive Gly-XY amino acid sequences, this domain is the core region for STAB1 to bind to ligands (such as acetylated low-density lipoprotein and bacteria) and is also involved in protein-protein interactions. b) EGF-like domain: Contains four epidermal growth factor-like repeats. This type of domain is commonly found in cell adhesion and receptor interactions. It contains up to 28 EGF-like repeats. This extra-long region may be involved in protein stretching and scanning, enabling it to efficiently capture ligands in the blood. c) Link domain: Contains two Link modules. This is another important hyaluronan-binding motif, further strengthening the high-affinity binding of STAB1 to HA.

Transmembrane region (2479-2499 aa): composed of one α-helix, its main function is to anchor the receptor on the cell membrane and transmit conformational changes in the extracellular region to the intracellular region.

Intracellular domain (2500-2570 aa): The sequence is short and contains potential signal transduction motifs, which may be involved in the regulation of intracellular signaling pathways after ligand binding (such as angiogenesis-related signals).

(Data source: protter)

STAB1 signaling pathways

STAB1 itself does not directly transmit typical intracellular signaling pathways . Its core function is endocytic clearance (scavenging). Its "signaling" is primarily manifested in indirectly regulating other signaling pathways through ligand internalization and synergizing with other signaling receptors. STAB1's most important "signal" is that its internalization function leads to changes in the extracellular environment, thereby indirectly affecting cellular status. LPS clearance pathway: STAB1 mediates the clearance and degradation of LPS (lipopolysaccharide). It binds to the HDL-LPS complex, initiating endocytosis (e.g., "coated pits and vesicles"), transporting LPS to early endosomes. Ultimately, LPS is inactivated and degraded in lysosomes by enzymes such as acid phosphatase/acid lipase/AOAH, thereby suppressing the inflammatory response.

(Data source: Kumar P et al. Cells. 2024)

STAB1 and disease

Sepsis-induced acute lung injury (ALI) field: In the macrophage regulatory pathway of sepsis-induced acute lung injury (ALI), STAB1 is involved in regulating the polarization process of macrophages, helping to promote the polarization of M2 macrophages with anti-inflammatory effects while inhibiting the polarization of pro-inflammatory M1 macrophages, thereby affecting acute lung injury (ALI) and may play a role in alleviating lung damage.

(Data source: Yang YH et al. Cell Death Dis. 2025)

Moyamoya disease (MDD): Moyamoya disease is a rare, chronic cerebrovascular disease characterized by progressive, bilateral stenosis or even occlusion of major blood vessels at the base of the brain, particularly the terminal internal carotid artery. Overexpression of STAB1 in human brain microvascular endothelial cells (HBMECs) enhances cell migration and angiogenesis, leading to thickening of the vascular intima, which also includes the media. Intimal thickening is a key pathological manifestation of MDD.

(Data source: Qin S et al. Int J Mol Med. 2025)

In the field of atherosclerosis, the scavenger receptors Stabilin-1 (Stab1) and Stabilin-2 (Stab2) are primarily expressed in liver sinusoidal endothelial cells. They are responsible for clearing circulating plasma proteins to maintain homeostasis and may influence atherosclerosis. Manta CP et al. found that in mice deficient in ApoE or Ldlr, genetic knockout or antibody inhibition of Stab1/Stab2 significantly attenuated Western diet-induced atherosclerosis, independent of changes in plasma lipid profiles. Plasma proteome analysis revealed alterations in multiple novel Stab1/2 ligands, including periostin, reelin, and TGFβi. Stab1/2 deficiency reprogrammed the monocyte transcriptome and suppressed the expression of the pro-atherogenic factor Egr1. These results suggest that targeting Stab1/Stab2 can systemically inhibit atherosclerosis by modulating the plasma proteome and innate immune responses, providing a new therapeutic strategy for this disease.

(Data source: Manta CP et al. Circulation. 2022)

High- grade serous ovarian cancer (HGSOC): Elorbany S et al., through single-cell sequencing in patients with high-grade serous ovarian cancer (HGSOC) and mouse models, found that neoadjuvant chemotherapy (NACT) induces increased expression of stabilin-1 in macrophages and FOXP3 in Treg cells. Inhibition of STAB1 activates anti-tumor macrophages, while FOXP3 antisense oligonucleotides (ASOs) reprogram Treg cells into effector T cells. In mouse models, combining chemotherapy with anti-stabilin-1 antibodies and/or Foxp3 ASOs significantly prolonged survival and progression-free survival and induced anti-tumor immune memory. This study suggests that targeting stabilin-1 and FOXP3 may enhance the efficacy of chemotherapy in HGSOC.

(Data source: Elorbany S et al. Nat Commun. 2024)

STAB1 Targeted therapy

Bexmarilimab is a targeted drug developed by Faron Pharmaceuticals Oy as a STAB1 monoclonal antibody . Its main mechanism of action is as a STAB1 inhibitor. It directly targets STAB1, enhancing the immune system's ability to kill target cells through antibody-dependent cell-mediated cytotoxicity (ADCC). It activates cytotoxic T lymphocytes and macrophages, enhancing anti-tumor immune responses. It is indicated for the treatment of acute myeloid leukemia, myelodysplastic syndrome, and solid tumors. It was approved for Phase 2 clinical trials on December 3, 2018.

(Data source: Rannikko JH. Cell Rep Med. 2023)

(Data source: Hollmén M. Mol Cancer Ther. 2022）